3-(Hydroxymethyl)chromones

ABSTRACT

The present invention relates to compounds of type I:   wherein R1 and R2 are hydrogen, halogen, alkyl, aralkyl, aryl, alkoxy, acylamino, hydroxy, or taken together R1 and R2 form an aromatic ring. These compounds are prepared from the corresponding o-hydroxy- omega -(methylsulfinyl)acetophenones. These compounds are useful in alleviating allergic manifestations.

United States Patent 191 Von Strandtmann et al.

[ June 3, 1975 3-(HYDROXYMETHYL)CHROMONES [75] Inventors: Maximilian Von Strandtmann,

Rockaway; John Shavel, Jr., Mendham; Sylvester Klutchko, Hackettstown; Marvin Cohen, New Milford, all of NJ.

[73] Assignee: Warner-Lambert Company, Morris Plains, NJ.

[22] Filed: Dec. 26, 1973 [21] Appl. No.: 428,290

Related U.S. Application Data [60] Division of Ser. No. 309,329, Nov. 30, 1972, Pat. No. 3,798,240, which is a continuation-in-part of Ser. No. 112,765, Feb. 4, l97l, abandoned.

[52] U.S. Cl 260/345.2; 424/283 [5 l Int. Cl C07d 7/34 [58] Field of Search 260/3452 References Cited UNITED STATES PATENTS 3,798,240 3/1974 von Strandtmann et al. 260/3452 Primary ExaminerJ0hn M. Ford Attorney, Agent, or Firm-Albert l-l. Graddis; Frank S. Chow; Anne M. Kelly [57] ABSTRACT The present invention relates to compounds of type I:

10 Claims, No Drawings 1 3-(HYDROXYMETHYDCHROMONES wherein R, and R each represent hydrogen, halogen, alkyl, aralkyl. aryl. alkoxy. acylamino, hydroxy or, taken together. R, and R form an aromatic ring.

The present invention also includes within its scope novel processes for the production of these 3-(hydroxymethyl)chromones.

As used throughout the specification and claims, the term alkyl and the alkyl" portion of alkoxy" embraces both straight and branched alkyl radicals containing from 1 to 8 carbon atoms; for example, methyl, ethyl, propyl. isopropyl. n-butyl. n-amyl. n-hexyl, 2- ethylbutyl, 2.3-dimethylbutyl and the like. The term halogen encompasses fluorine, bromine. chlorine and iodine. Ther term aryl denotes an aromatic hydrocarbon of 6 to 8 carbon atoms such as phenyl, tolyl and the like. The term aralkyl encompasses alkyl groups in which aryl as previously defined is substituted for a hydrogen atom, such as for example benzyl. phenethyl. and the like. The term acyl" means radicals of those hydrocarbon carboxylic acids of less than 12 carbon atoms as exemplified by the lower alkanoic acid, e.g.. acetic, propionic, butyric, the aryl carboxylic acid, e.g., benzoic and toluic acid and the like.

The compounds of this invention are active orally or by injection in preventing the allergic and asthmatic reactions in mammals such as cats, dogs. guinea pigs and the like. Thus, for example, in tests conducted accord ing to the procedures described in Life Sciences, 7, 465 (1963), and in Proc. Soc. Exptl. Biol. Med.. 81. 584 1952). the compounds of this invention when administered to the respective animals such as rats and guinea pigs at a dose of about to 100 mg/kg are capable of alleviating allergic and asthamatic conditions in these animals.

The compounds of this invention are useful in providing symptomatic relief of allergic conditions such as asthma, hay fever and the like. Generally speaking, these compounds are administered orally. by injection or in the form of an aerosol spray at a dose of about 5 to 100 mg/kg.

in order to use these compounds they are formulated with known pharmaceutical diluents such as water. lactose. powdered sugar, mannitol and the like into dosage forms such as tablets. capsules. and the like.

According to the present invention. these compounds are prepared by a reaction as represented in the following scheme:

2 9 9 51 cos SCH. 2 2 ca 0 R i Z c ase fi \Orl R III i. ii CH 0a m h 0 -ca SOH R 3 o 11 CHZOH I R I The desired compounds 1 are obtained from o-hydroxy-w-(methylsulfinyl) acetophenones with or without isolation of the intermediate compounds 11.

The starting compounds 111 are prepared by the reaction of salicylic esters with sodium methylsulfinyl carbanion generated by the action of sodium hydride on dimethyl sulfoxide. A similar preparation of compound 111 (R, and R H) has been reported. Becker, et al. JACS. 3410 (1963).

In order to further illustrate the practice of the invention the following examples are included:

EXAMPLE 1 i o 3on 1 CH 0a 2 3-(hydroxymethyl )-3( methylsulfinyl )-4-chromanone A quantity of 24.3 g (0.3 mole) of 37% aqueous formaldehyde solution was added all at once to a stirred. warm (40C) solution of 29.7 g (0.15 mole) of 2-hydroxy-2-(methylsulfinyl) acetophenone, g potassium carbonate and 600 ml of water. After 1 minute turbidity developed as an oil separated. The mixture was allowed to cool slowly over a period of one-half an hour. The oil was extracted into 5 liters of ether and the solution was dried (K CO filtered and concentrated to give 25.0 g (69.4%) of a viscous oil N 1.5868.

Anal. Calcd for C I-1, 0 5: C. 54.99; H, 5.03; S. 13.34.

Found: C. 55.06: H. 5.15; S, 13.09.

EXAMPLE 7 3-( hydroxymethyl )chromone A solution of 14.0 g (0.058 mole) of 3- (hydroxymethyll-3-(methylsulfinyl)-4-chromanone in 30 ml of toluene was refluxed vigorously for 10 minutes. The cooled solution yielded 5.1 g (49.5%) of pale yellow crystals, mp l08-ll0C. Purematerial, mp 109ll1C, was obtained by recrystallization from ethyl acetate-petroleum ether.

Anal. Calcd for C H O C, 68.18; H, 4.58.

Found: C, 68.20: H, 4.68.

EXAMPLE 3 6-hydroxy-3( hydroxymethyl )-3-( methylsulfinyl )-4- chromanone.

This compound was prepared by reacting 8.56 g of 2, '-dihydroxy-2-(methylsulfinyl)acetophenone with 20 ml of formalin in analogous fashion to 3- (hydroxymethyl)-3-(methylsulfinyl)-4-chromanone. The material was recrystallized from methanol, mp l5660 C; yield 1 g Anal. Calcd for C, H, O S: C, 51.55; H, 4.72; S.

Found: C, 51.73; H, 4.78; S, 12.30.

EXAMPLE 4 l l H U cn on 6-hydroxy-3-(hydroxymethyl)chromone. This was prepared by boiling the 6-hydroxy-3- (hydroxymethyl)-3-(methylsulfinyl)-4-chromanone.

obtained from 10.56 g of 2,5-dihydroxy-2-(methylsulfmyl)acetophenone in 200 ml of xylene for min. The

mixture was chilled, the solid filtered off and recrystal lized from CH OH, m.p. 2l5l8.5C; yield 0.5 g

Anal. Calcd for C H O C. 62.50, H, 4.20.

Found: C, 62.48; H. 4.32.

EXAMPLE 5 t if i l CH3 01 g cir on 6-chloro-3-(hydroxymethyl)-3-(rnethylsulfinyl)-4- chromanone EXAMPLE 6 CH OH 6chloro-3-(hydroxymethyl )chromone.

To a solution of g of K CO in 200 ml of H 0 was added with stirring 14 g of 5-chloro-2'-hydroxy-2-(methylsulfinyl) acetophenone. The yellow solution that formed was then treated with stirring with 34 ml of formalin. On further stirring an oil precipitated which solidified. The mixture was chilled, and the precipitate was filtered off and washed with cold H O. The precipitate was suspended in 300 ml of xylene and the mixture boiled for /a hour with charcoal. The mixture was filtered hot and on cooling crystals formed in the filtrate. These crystals were filtered off'and recrystallized from absolute ethanol, mp 163--64; yield 6 g (49%).

Anal. Calcd for C H ClO C, 57.03; H, 3.35. Found: C, 57.00; H, 3.23.

EXAMPLE 7 3-(hydroxymethyl)-6-iodo-3-(methylsulfinyl)-4- chromanone To asolution of 20 g of K CO in ml of H 0 was added 9.75 g of 2-hydroxy-5 -iodo-2-(methylsulfinyl) acetophenone.. The resulting solution was treated with 17 ml of formalin and after 15 mins. stirring the solid that precipitated was filtered, washed with cold H O.

6 and recrystallized from acetone. mp 122-24z yield 4 was recrystallized from absolute ethanol, mp g (36%). 15053.5; yield 3.5 g (56%).

Anal. Calcd for C H IO,S: C, 36.08; H. 3.03; S, Anal. Calcd for C H ,O,: C, 64.07; H. 4.89. 8.76. Found: C, 64.21; H. 4.86. Found: C. 36.30; H. 3.01; S, 8.86.. 5.

, EXAMPLE 11 EXAMPLE 8 O 9 f l 10 $CH l L l 3 I CH OH Br CH OH I 3-(hydroxymethyl)-6 iodochromone. 6-bromo-3-(hydroxylnethyl)-3-(methylsulfinyl)4- This was prepared by reacting a solution of g of Chromanone' 2'-hydroxy-5'-iod0-2-(methylsulfinyl)acetophenone in To a solution of 40 g of K CO in 200 ml of H 0 is 200 ml of H 0 containing 40 g of K CO 'with 34 ml of 20 added with stirring 16.6 g of 5'-bromo-2'-hydroxy2- formalin in analogous fashion to 6-chloro-3-(hydrox- (methylsulfinyl) acetophenone. The resulting solution ymethyl)chromone. Thematerial was recrystallized is then treated with 34 g of formalin. After 15 mins. from absolute ethanol, mp 13437; yield 5 g (27.5%). stirring, the solution becomes cloudy and an oil precipi Anal. Calcd for C H lO C, 39.76; H, 2.34. tates. On further stirring the oil solidified. The mixture Found: C, 39.88; H, 2.40. is chilled, the precipitate filtered, washed with cold H 0, and recrystallized from acetone, mp 129-3l; EXAMPLE yield 5g (26%).

Anal. Calcd for C H BrO,S: C, 41.39; H, 3.47; S, 10.05.

30 Found: c, 41.73; 11, 3.43; 5, 10.18. I CH OH 2 EXAMPLE 12 CH l 3-(Hydroxymethyl)-6-methoxy-3r(methylsulfinyl)-4- T/\-CH7OH chromanone. l This was prepared by reacting a solution of 14g of 40 2'-hydroxy-5'-methocy-2-(methylsulfinyl)acetophenone in 200 ml of H 0 containing 40 g of K CO with 34 ml of formalin in analogous fashion to 6-ch1oro-3- 6-bromo'3'(hydroxymethynchmmone' (hydroxymethyl)-3-(methylsulfinyl)chromanone. The 4 To a solution of 15.6 g of K CO in 78 ml of H 0 is material was recrystallized from acetone, mp 5 added 6.5 g of 4-bromo-2'-hydroxy-2-(methylsulfinyl) l071 10 C.; yield 4 g 25%). acetophenone. The resulting solution was then treated Anal. Calcd for C H O S: C, 53.32; H, 5.22; S, with stirring with 13.3 g of formalin. After several min- 1 1.86. utes of stirring, an oil precipitated which solidified on continued stirring. The mixture is chilled and the precipitate filtered and washed with cold H O. The precip- EXAMPLE 10 itate was then suspended in 50 ml of xylene and the mixture boiled for V2 hr. The resulting solution was cooled and the crystals that formed were filtered and A O recrystallized from absolute ethanol with the aid of Found: C, 53.53; H, 5.22; S, 11.78.

charcoal, mp 154-58; yield 1 g (17% Anal. Calcd for C H BrO C, 47.09; H, 2.77.

CH3, \I(\ Found. c, 47.29, H, 2.81.

0 EXAMPLE l3 3-( hydroxymjethyl )-6-methoxychro1none.

C1 0 Thls materlal was prepared by reactlng a solutlon of I l 7 g of Zf-hydroxy-S-methoxy-2-(methylsulfinyl)- 6s I l 4 acetophenone in '100 ml H O containing 20 g of i CHZOH K CO with 17 ml of formalin in analogous fashion to 6-chloro -3-lhydroxymethyll chromone. The material 7-chloro-3-(hydroxymethyl)chromone.

This material was prepared by reacting a solution of 14 g of 4-chloro-2'-hydroxy-2-(methylsulfinyl) acetophenone in 200 ml of H containing 40 g of K CO in analogous fashion to 6-chloro-3-(hydroxymethyl)chromone. The material was recrystallized from absolute ethanol. mp l57-59; yield 6 g (47% Anal. Calcd for C ,H;ClO C. 57.03; H. 3.35. Found: C, 57.06; H, 3.32.

EXAMPLE 14 3-( hydroxymethyl )-8-isopropylchromone..

To a solution of 28 g of K. ,CO in 140 ml of H 0 was added 10 g of 2'-hydroxy-3'-isopropyl-2-(methylsulfinyl)acetophenone. The resulting suspension was then treated with stirring with g of formalin. A clear solution formed which on further stirring becomes cloudy and an oil precipitated out. The mixture was extracted 4 times with 25 ml portions of CH Cl and the combined CH Cl extracts were dried over N21 SO and taken down to a gum under reduced pressure. The gum was taken up in 50 ml of toluene and the solution boiled for V2 hour. On cooling, crystals formed. The crystals were filtered and recrystallized from toluene. mp l2l23; yield 4 g (44%).

Anal. Calcd for C H O C, 71.54; H, 6.47. Found: C, 71.71; H, 6.46.

EXAMPLE l5 hydroxymethyl )-7-methoxychromone.

This was prepared by reacting 2 g of 2- y ymethoxy-2-(methylsulfinyl)acetophenone wi ml of formalin in analogous fashion to the prepar of 3 -(hydroxymethyl)-8-isopropylchromone. Th millerial was recrystallized from absolute ethanol, m.p. ll7.5-18.5 C.; yield 0.5 g (29%).

Anal. Calcd for C H O C, 64.07; H, 4-

Found: C, 64.28; H, 4.79.

EXAMPLE l6 TCH EXAMPLE 17 Y CH OH 8-chloro-3-(hydroxymethyl)chromone.

This was prepared by reacting a solution of 14 g of 3 '-chloro-2 '-hydroxy-2-(methyIsulfinyl)acetophenone in 200 ml of H20 containing 40 g of K CO with 34 ml of formalin in an analogous fashion to 3- hydroxymethyl)-8-isoprop,ylchromone. The material was recrystallized from absolute ethanol, rap/158- 62; yield 6 g (47%).

Anal. Calcd for c,,,H,c'/o,; c, 57.03; H, 3.35. Found: C, 57.18; H, 3.34. I v

EXAMPLE l8 7-acetamido-3-( hydroxymethyl )chromone.

To a solution of 23.5 g of K CO in I20 ml of H 0 is added 9 g of 4-acetamido-2-hydroxy 2-(methylsulfinyUacetophenone. The solution is then treated .with 20 ml of formalin and after about 15mins. stirring, the Crystalline precipitate that forms is filtered, washed with cold H 0, and recrystallized from acetone. The crystalline product is taken up in 20 ml of dirnethyl formamide and the solution boiled for 15 min. The solution is diluted to 125 ml with CH CN, and on chilling crystals deposited. The crystals are filtered and recrystallized from CH CH, mp 25458; yield. 1 g (12%). Anal. Calcd for C H1 NO C, 61.80; H, 4.75; N, 6.01. Found: C. 61.97; H, 4.80; N, 6.02.

EXAMPLE 19 6,8-dibromo-3-(hudroxymethyhchromone.

To a solution of 8 g of K CO in 40 ml of H is added 4.2 g of 3',5'-dibromo-2-hydroxy-2-(methylsulfinyl)acetophenone. The solution is then treated with 6.8 ml of formalin and stirred for min. A gum precipitates. The supernatant liquid is decanted, and the gum washed with cold H O by decantation and then triturated with cold CH OH, causing it to solidify. The solid is filtered, washed with cold CH OH, and suspended in ml of toluene. This is boiled for 15 min. The resulting solution is cooled and the crystalline precipitate is filtered off, washed with cold toluene, and recrystallized from absolute ethanol, mp l6669; yield 0.5 g (12.5%).

Anal. Calcd for C H Br O C, 35.96; H, 1.81.

.Found: C, 35.98; H, 1.87.

EXAMPLE 20 3-( hydroxymethyl )benzo[h]chromone A mixture of 2.0 g (0.0081 mole) of 1'-hydroxy-2- (methylsulfinyl)-2'-acetonaphthone, 2.63g(0.032 mole) of 37% aqueous formaldehyde, 20 ml of methanol and 10 g potassium carbonate was warmed to 50 for 5 minutes. Water (50 ml) was added and the reaction was again warmed at 50 for 5 minutes. Additional potassium carbonate was added to salt out" organic layer. Some of the methanol was stripped off and the mixture was extracted with 30 ml toluene and 100 ml of methylene chloride. The solution was dried over potassium carbonate, filtered and stripped of methylene chloride. The remaining toluene solution was refluxed for one half hour. On cooling, yellow crystals separated. Wt. 0.5 g (27%) mp l624C. Recrystallization from ethyl acetate gave pure material, mp l635C.

Anal. Calcd for C H O C, 74.33; H, 4.46.

10 Found: C, 74.42; H, 4.49.

EXAMPLE 21 6-Fluoro-3-( hydroxymethyl )chromone.

This compound was prepared by allowing to react a solution of 13 g. of 5-fluoro-2-(methylsulfinyl)- acetophenone in 400 ml. of H20 and 40 g. of K CO with 34 ml. of formalin in analogous fashion to 6- bromo-3-(hydroxymethyl)chromone. The material was recrystallized from abs. ethanol; m.p. 153- l56; yield 3.5 g. (30%).

Anal. Calcd for C H FO C, 61.86; H, 3.63. Found: C, 61.63; H, 3.61.

EXAMPLE 22 3-(Hydroxymethyl)-4-naphtho[2,3-b1pyran-4-one.

A solution of 20.0 g. (0.081 mole) of 3-hydroxy-2- (methylsulfinyl)-2-acetonaphthone, 400 ml of methanol, 19.71 g. (0.24 mole) of 37% formaldehyde and 20 drops of piperidine was maintained at reflux for 15 minutes and concentrated. Toluene (300 ml.) was added to the residue and the mixture was heated to reflux. The resulting solution was decanted from a small amount of undissolved material and reheated to reflux for /6 hr. Crystals separated from the cooled solution; wt, 5.4 g. (30%); m.p. 165168. Recrystallization from toluene gave pure, orange crystals; m.p. l74--l76.

Anal. Calcd. for C H O C, 74.33; H, 4.46. Found: C, 74.52; H, 4.60.

3-(Hydroxymethyl)-6-( l ,1,3,3-tetramethylbutyl)chromone.

To a solution of 20 g. of K CO in 200 ml. of H 0 was added 9 g. of 2-hydroxy-2-(methylsulfinyl)-5'- (1,l,3,3-tetramethylbutyl)acetophenone with stirring. The mixture was treated with 25 ml. of methanol followed by 17 ml. of formalin. After 10 min. of stirring. an oil precipitated out. The mixture was extracted 3 times with 50 ml. portions of CH Cl Combined extracts were dried over Na,so,, and concentrated to a gum under reduced pressure. The gum was taken up in ml. of xylene, and the solution was boiled for 15 min. The xylene solution was evaporated at reduced pressure and the mixture was recrystallized from Skelly B. m.p. 99l01; yield 2.5 g. (14.5%).

Anal. Calcd. for C H Q C, 74.97; H. 8.39. Found: C. 75.26; H. 8.57.

EXAMPLE 24 3 Hydroxymethyl )-8phenylchromone.

To a solution of 40 g. of K CO in 400 ml. of H was added 16.46 g. of 2'-hydroxy-2-(methylsulfinyl)-3'- phenylacetophenone. The stirred suspension was treated with 34 ml. of formalin, and a clear solution formed. After 10 min. a gum started to come out of solution. The mixture was stirred for an additional min. and extracted 5 times with 100 ml. portions of CH Cl- Combined extracts were dried over Na- SO and evapo rated to a solid residue under reduced pressure. The residue was taken up in 100 ml. of toluene, and the mixture boiled for 30 min. The resulting solution was chilled, and the crystalline precipitate that formed was filtered off, and recrystallized from benzene; m.p. 105107; yield 4 g. (27%).

Anal. Calcd. for C H O C, 76.18; H. 4.79. Found: C, 76.07; H, 4.83.

EXAMPLE 3-(Hydroxymethyl)-8-methylchromone.

To a solution of 60 g. of K CO in 600 ml. of Hf) was added with stirring 19.2 g. of 2'-hydroxy-3-methyl-2- (methylsulfinyl)acetophenone. The yellow suspension was treated with 51 ml. of formalin, and a clear solution was obtained. After 15 minutes of stirring an oil separated out. The mixture was extracted 3 times with 100 ml. portions of CH Cl Combined CH Cl extracts were dried over Na SO and evaporated to an oil under reduced pressure. The oil was taken up in 250 ml. of toluene, and the mixture boiled for V2 hr. The resulting solution was chilled and the crystals that formed filtered off and recrystallized for absolute ethanol; m.p. 142144; yield 9.5 g. (53%).

Anal. Calcd. for C H O C, 69.56; H, 5.30. Found: C 69.56; H, 5.49.

EXAMPLE 26 3-( Hydroxymethyl )-6.8-dimethylchromone.

To a solution of 60. g. of K CO in 600 ml. of H 0 was added with stirring 20.75 g. of 2'-liydroxy-3',5'- dimethy1-2-(methylsulfiny1)acetophenone. The suspen sion was treated with 51 ml. of formalin. and a clear solution was obtained; After 10 min. stirring an oil separated out which solidified. The mixture was chilled. and the solid filtered. washed with cold H 0. and suspended in 375 ml. of toluene. The mixture was boiled for 30 min. and the resulting solution chilled. A crystalline precipitate formed. This was filtered. and recrystallized from CH CN; m.p. l80.5183; yield 11.5 g. (63% Anal. Calcd. for C H, O C. 70.57; H. 5.92. Found: C. 70.40, H, 6.07.

EXAMPLE 27 i Q t. k cmoa. I

3-( Hydroxymethyl)-6-phenylchromone.

To a solution of 40 g. of K CO in 400 ml. of H 0 was added 16.4 g. of 2'-hydroxy-2-(methylsulfinyl)-5'- phenylacetophenone. The resulting yellow solution was treated with 64 ml. of formalin with stirring. After 10 min. a heavy oil deposited. The mixture was extracted 3 times with ml. portions of CHCI Combined extracts were dried over Na- SO and concentrated to an oil under reduced pressure. The oil was taken up in 200 ml. of toluene, and the solution boiled for 30 min. On cooling crystals deposited. The crystals were filtered, and recrystallized from benzene, m.p. 130.5-l32; yield 5 g. (33%).

Anal. Calcd. for c -r 0 C, 76.19; H, 4.80. Found: C, 76.03; H, 4.93.

EXAMPLE 28 ciao w l CH2 on cn ci ii 3-( Hydroxymethyl )-5,7-dimethoxychromone.

EXAMPLE 29 EXAMPLE 3O 3-( Hydroxymethyl )-6-methylchromone.

This compound was prepared by allowing to react a solution of 12.72 g. of 2-hydroxy-5'-methyl-2-(methylsulfinyl)acetophenone in 400 ml. of H and 40 g. of K. ,CO with 34 m1. of formalin in analogous fashion to 6-bromo-3-(hydroxymethyl)chrom0ne. The material was recrystallized from methanol. m.p. l43l47; yield 4.5 g. (39%).

Anal. Calcd. for C H O C, 69.46; H. 5.30. Found: C, 69.21; H, 5.30.

EXAMPLE 31 CHJQ L ca,oa

3-( Hydroxymethyl )-5-meth0xychromone.

To a solution of 14 g. of 2'-hydroxy-6-methoxy-2- (methylsulfinyl)acetophenone in 200 ml. of H 0 containing 40 g. of K CO was added 34 ml. of formalin, and the solution stirred for min. An oil separated out, and the mixture was extracted 3 times with 50 m1. portions of CH Cl Combined extracts were dried over Na SO and concentrated to an oil under reduced pressure. The oil was taken up in 250 ml. of toluene, and the mixture boiled for min. On cooling, crystals formed. These were filtered and recrystallized from ethylacetate; m.p. 155156; yield 3 g. (25%).

Anal. Calcd. for C ll .,O :C, 64.07: H, 4.89. Found: C, 63.81; H, 4.94.

EXAMPLE 32 0 (crow cazoa 6.8-di-tert-but vl-3-( hydroxymethyl )chromone.

To a solution ol4t) g. of K- ,CO;, in 300 ml. ofH O was added with stirring 18.6 g. of 3'.5'-diterthut vl-2'- hydroxy-2-(methylsulfinyl)acetophenone. The resulting suspension was treated with 64 ml. of formalin which resulted in an almost clear solution. After 15 min. of stirring, an oil separated out. The mixture was extracted 3 times with ml. portions ofCHCl Conibined extracts were dried over Na SO and concentrated to an oil under reduced pressure. The oil was taken up in ml. of toluene. and the mixture boiled for 30 min. On coolinig, crystals formed. The crystals were filtered off. and recrystallized from ethylacetate; m.p. 156158; yield 5 g. (29% 1.

Anal. Calcd. for C H O C, 74.97; H. 8.39. Found: C, 74.68; H. 8.54.

We claim:

1. A compound of the formula:

CH OH soca wherein R and R are each a member selected from a group consisting of hydrogen. lower alkyl of 1 to 6 carbon atoms. halogen, carbocylic aryl of 6 to 8 carbon atoms, aryl lower alkyl in which aryl and lower alkyl are as defined, alkoxy of 1 to 6 carbon atoms, hydroxy, acylamino in which acyl is alkanoyl ofless than 12 carbon atoms, and R and R when attached to adjacent carbon atoms, together form an orthofused arylene ring in which aryl is as defined.

2. A compound according to claim 1 which is 3- (hydroxymethyl)-3-(methylsulfinyl)-4-chromanone.

3. A compound according to claim 1 which is 6- hydroxy-3-(hydroxymethyl)-3-(methylsulfinyl)-4- chromanone.

4. A compound according to claim 1 which is 6- chloro-3-(hydroxymethyl)-3-(methylsulfinyl)-4- chromanone.

5. A compound according to claim 1 which is 3- (hydroxymethyl)-6iodo-3-(methylsulfinyl)-4- chromanone.

6. A compound according to claim 1 which is 3- (hydroxymethyl)-6methoxy-3-(methylsulfinyl)-4- chromanone.

7. A compound according to claim 1 which is 6- bromo-3-(hydroxymethyl)-3-(methylsulfinyl)-4- chromanone.

8. A compound according to claim 1 which is 3- (hydroxymethyl)-6-methyl-3-(methylsulfinyl)-4- chromanone.

9. A compound according to claim 1 which is 2.3- dihydro-3-(hydroxymethyl)-3-(methylsulfinyl)-4H- naphtho[ 1 ,2-blpyran-4-one.

10. A compound according to claim 1 which is 2.3- dihydro-3-(hydroxymethyl)-3-(methylsulfinyl)-4H- naphtho[2,3-b]pyran-4-one. 

1. A COMPOUND OF THE FORMULA:
 1. A compound of the formula:
 2. A compound according to claim 1 which is 3-(hydroxymethyl)-3-(Methylsulfinyl)-4-chromanone.
 3. A compound according to claim 1 which is 6-hydroxy-3-(hydroxymethyl)-3-(methylsulfinyl)-4-chromanone.
 4. A compound according to claim 1 which is 6-chloro-3-(hydroxymethyl)-3-(methylsulfinyl)-4-chromanone.
 5. A compound according to claim 1 which is 3-(hydroxymethyl)-6-iodo-3-(methylsulfinyl)-4-chromanone.
 6. A compound according to claim 1 which is 3-(hydroxymethyl)-6-methoxy-3-(methylsulfinyl)-4-chromanone.
 7. A compound according to claim 1 which is 6-bromo-3-(hydroxymethyl)-3-(methylsulfinyl)-4-chromanone.
 8. A compound according to claim 1 which is 3-(hydroxymethyl)-6-methyl-3-(methylsulfinyl)-4-chromanone.
 9. A compound according to claim 1 which is 2,3-dihydro-3-(hydroxymethyl)-3-(methylsulfinyl)-4H-naphtho(1,2-b)pyran-4 -one. 